The iron-binding pseudoglobulins collectively called transferrins or siderophilins comprise a class of proteins with strikingly similar features. X-ray crystallographic analyses of human lactoferrin (Anderson, B. F. et al. (1987) Proc. Natl. Acad. Sci. USA 84:1769-1773) and rabbit serum transferrin (Bailey, S. et al. (1988) Biochemistry 27:5804-5812) reveal that these proteins consist of two similar lobes connected by a short bridging peptide and that each lobe contains two domains defining a deep cleft containing the binding site for a metal ion and a synergistic anion.
The chicken ovotransferrin gene has been expressed in transgenic mice (McKnight, G. S. et al. (1983) Cell (Cambridge, Mass.) 34:335-341) and a fusion protein of part of rat transferrin with galactosidase has been expressed in E. coli (Aldred, A. et al. (1984) Biochem. Biophys. Res. Commun. 122:960-965). Except for this fusion protein, attempts to express transferrin or portions of the molecule in prokaryotic systems have been unsuccessful (Aldred, A. et al. (1984) Biochem. Biophys. Res. Commun. 122:960-965). The highly convoluted structure of the protein and large number of disulfide bridges in the molecule are probably the major impediments to expression in bacterial hosts. Attempts to mimic partially the natural protein folding environment by targeting the protein for bacterial membrane transport via an attached alkaline phosphatase signal sequence have been unsuccessful.